POS1060 HUMORAL RESPONSES AGAINST HDL ARE LINKED TO LIPOPROTEIN TRAITS, ATHEROSCLEROSIS, INFLAMMATION AND PROTEOMIC PATHOGENIC PATHWAYS DURING EARLY ARTHRITIS STAGES
Authors: J. Rodríguez-Carrio, M. Alperi-López, P. López, Á. Pérez-Álvarez, G. Robinson, S. Alonso Castro, N. Amigó, F. Atzeni, A. Suárez
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> cardiovascular (CV) risk excess in rheumatoid arthritis (RA) cannot be solely attributed to traditional CV risk factors. Chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis development in RA. Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL) and its components. However, their exact specificity, clinical relevance and emergence along disease course are unknown, especially during the earliest phases of arthritis. <h3>Objectives</h3> to characterize the specificity and clinical relevance as predictors of anti-HDL responses along during the earliest phases of arthritis. <h3>Methods</h3> IgG and IgM serum levels of antibodies against HDL (anti-HDL) and Apolipoprotein A1 (anti-ApoA1) were measured in 82 early RA patients (EULAR/ACR classification criteria), 14 arthralgia individuals (EULAR definition) and 96 controls. Established RA patients (n=42) were included for validation. Atherosclerosis occurrence and vascular stiffness were measured by Doppler-ultrasound. Lipoprotein content, particle numbers and size were measured by H-NMR. Cytokines were measured by immunoassays. A cardiometabolic-related protein panel was evaluated using high-throughput targeted proteomics. <h3>Results</h3> IgG and IgM anti-HDL and anti-ApoA1 responses were increased in early RA compared to controls (both p&lt;0.001) and were comparable to established disease. Only IgG anti-ApoA1 antibodies were increased in arthralgia compared to controls (p&lt;0.050). IgG anti-HDL and anti-ApoA1 were associated with unfavourable lipoprotein traits (particle content, number and size distribution) in RA and arthralgia, respectively. A similar picture was observed for positive correlations with inflammatory mediators (IFNa, MIP-1a, IL-6, IL-8 and IFNg). No associations with clinical features or traditional risk factors were found. IgG anti-HDL were independently associated with atherosclerosis occurrence (p=0.012) and extension (r=0.274, p=0.016) in early RA. This association remained after adjusting for traditional CV risk factors in multivariate models (OR 1.001 [95% CI: 1.000 – 1.002], p=0.004). The addition to IgG anti-HDL to the mSCORE chart improved patient classification and outperformed patient stratification over mSCORE alone (Table 1). The addition of IgG anti-ApoA1 levels resulted in low-to-milder improvements (Table 1). IgG anti-HDL antibodies correlated with serum proteomic signatures involved in immune activation, remodelling, and lipid metabolism pathways in early RA (Figure 1). <h3>Conclusion</h3> humoral responses against HDL particles are an early event along arthritis course, although quantitative and qualitative differences can be noticed among stages. These differences informed distinct capacities as biomarkers (incremental value) and underlying pathogenic circuits. Anti-HDL but not anti-ApoA1 were robust predictors of lipoprotein features, inflammatory milieu and subclinical CV burden in early RA. <h3>Acknowledgements</h3> ISCIII (PI21/00054), ISPA (2021-046-INTRAMURAL NOV-ROCAJ), EULAR (Q122RSV03) <h3>Disclosure of Interests</h3> None Declared.